The Human Microbiome Project has revealed the composition of adult human microbial communities at the level of species, but how they are acquired and how stable they are is not well understood. Community sequencing studies have shown relative levels of taxa to fluctuate over time at multiple body sites, but in the gut and urinary tract, membership of human microbial communities shows considerable stability over the long term. This suggests that the human microbiome is a stable feature with implications for disease and health similar to that of our human genome. This important potential determinant of oral health needs to be investigated starting with the initial acquisition of the oral microbiota. e have recently demonstrated a robust assembly of a common core set of species in human infants that is resistant to disruption by a number of environmental perturbations. This remarkable specificity demonstrates a surprisingly robust process and suggests a biologic blueprint for acquisition of the oral microbiome, and some potential drivers have a human genetic basis. We hypothesize that each human harbors a set of strains/species that is particularly well adapted to his or her specific genetically determined environment, and that these bacteria are a better fit for genetic offspring than those harbored by unrelated individuals. If so, the human microbiome may be another form of heritable genetic material passed from parent to offspring -- another sort of epigenetics. In aim 1 we will elucidate the natural histor of acquisition of the oral microbiome from infancy to adolescence and measure stability of microbial community membership over two years. In aim 2 we will determine the contribution of genetics to bacterial transmission from mothers to babies by comparing biologic and adoptive mother-child dyads. We will determine relative levels of bacterial species using 454 pyrosequencing of the 16S rRNA gene. Comprehensive analysis of strains has just become technically feasible, and this will allow us to elucidate stability, assembly of the oral microbiom and transmission at a new level of resolution. We will determine strain variation by metagenomic sequencing and mapping of bacterial sequences to reference genomes and determining single nucleotide polymorphisms (SNPs). The proposed studies will elucidate the assembly of oral microbial communities from birth through adolescence. They will reveal the complexity of the microbiome at the level of species and strain, the extent to which humans share a core set of species and strains, their stability over time and in response to perturbations, and to what extent the human oral microbiome is a heritable feature, similar to our human genome. These findings will have major implications for disease and health including possible determinants of disease susceptibility, risk assessment and feasibility of strategies for prebiotic/probiotic therapies.